During recent months, an outbreak of Zika virus infection has been spreading through the Americas. Drs. Chen and Hamer provide a timely and practical update on this infection.

HISTORY

The virus was first isolated from a monkey being used for yellow fever surveillance in the Zika Forest of Uganda in 1947. Subsequent serologic surveys suggested that the virus was present in both Africa and Asia, but reports of human infection were uncommon until 2007. Then, the virus was associated with an outbreak of a febrile illness on Yap Island in Micronesia. (See the September 2007 issue of Infectious Disease Alert.) In late 2013, the virus was identified in French Polynesia and accounted for approximately 19,000 cases. In early 2015, the virus was identified in patients with a dengue-like illness in Brazil. The Brazilian outbreak has subsequently spread and is circulating in more than 20 countries/territories within the Americas and is being carried by travelers to other parts of the world.

VIRUS

Zika is an RNA flavivirus related to the viruses responsible for dengue, yellow fever, West Nile, and Japanese encephalitis. There are two major lineages of the virus: African and Asian. Outbreaks in the Pacific and in the Americas are due to the Asian lineage of Zika virus.

VECTORS

Zika is transmitted by Aedes mosquitoes. Different Aedes species have been involved in different outbreaks. Aedes aegypti and Aedes albopictus are present in much of the Americas, including areas in the southern United States. Aedes mosquitoes also transmit dengue and chikungunya, so the geographical distribution of these infections overlaps. The mosquitoes usually bite during the daytime.

CLINICAL PRESENTATIONS

Up to 80% of infected individuals have no clinical manifestations of Zika. Those who are symptomatic have clinical presentations approximately 2-7 days after a bite from an infected mosquito. They have a maculopapular rash for 2-14 days (median duration of rash: 6 days), arthralgia for 1-14 days (median duration of arthralgia: 3.5 days), and conjunctivitis. Myalgia, headache, retro-orbital pain, joint swelling, vertigo, and vomiting are also sometimes reported. The illness is self-limited and usually resolves within a week. (Conversely, the arthralgia of chikungunya can begin similarly but can persist for many months.) Neurologic and autoimmune complications (Guillain-Barre syndrome) were identified during the outbreak of Zika in French Polynesia. Microcephaly was frequently reported in the current Brazilian outbreak.

DIAGNOSIS

Serological tests for dengue and Zika cross-react, so false-positive results for either infection are possible with infection by the other virus. Viremia occurs for up to 11 days following the onset of symptoms, and RT-PCR tests can confirm the diagnosis during the first week of infection. Zika RNA can be detected in saliva and urine for longer than it can be detected in blood.

MANAGEMENT

Supportive care should be provided for patients with Zika infection. Ibuprofen and other non-steroidal agents are usually avoided since they might diminish platelet function in patients who are already thrombocytopenic due to the infection. Acetaminophen may be used.

PREVENTION

There is no vaccine to prevent Zika infection. Prevention of Zika infection is based on mosquito avoidance. Pregnant women should avoid travel to areas where Zika is active. Repellents containing DEET or picaridin are effective. Insecticides and drainage of mosquito breeding areas are similarly appropriate.

COMMENTARY

The spread of Zika beyond Africa prompted concern for Zika as an “emerging infection” in 2009.1 Now, news media have popularized dramatic concerns about Zika infection. International organizations are publicizing the “global emergency” status of Zika virus.2 Countries are seeking billions of dollars of funding to counter the spread of Zika. Meanwhile, the Centers for Disease Control and Prevention (CDC) website is frequently updated with current scientifically sound information.3

As viruses spread geographically, the vectors and clinical manifestations can change. This has been seen with yellow fever, West Nile virus, and chikungunya, so it is not surprising that different mosquito vectors and different clinical situations are seen as Zika spreads.4 If Zika gets established in U.S. populations of Aedes aegypti, it could potentially spread west from Florida and Georgia to Texas, and even to parts of New Mexico, Arizona, and California. If the virus spreads in American populations of Aedes albopictus, it could spread up the eastern half of the United States as far north as Iowa, Illinois, Indiana, Ohio, and Pennsylvania. (CDC maps show more detail of Aedes distribution.5)

Zika infection is usually asymptomatic, and symptomatic patients usually have a mild illness that resolves within a week. However, risks of two serious complications have heightened concern for spreading Zika infection. First, Guillain-Barre syndrome was reported during the Polynesia outbreak of Zika in 2013. Ongoing surveillance will help determine whether the current American outbreak of Zika is also associated with autoimmune neurologic consequences. Second, there is a possible (not yet definitively proven to be causal) association between Zika and microcephaly. Among the first 35 cases of microcephaly reported from areas of actively circulating Zika virus to a new registry in Brazil, 74% of mothers reported having a rash during pregnancy.6 Two patients who died in the immediate neonatal period and two miscarried babies had Zika virus RNA isolated from multiple body tissues; mothers were from Zika-active areas of Brazil and reported febrile illnesses with rash during pregnancy.6 Brazilian infants with Zika-related microcephaly have had eye changes, including mottling of macular pigment and chorioretinal atrophy, as well as optic nerve changes, including hypoplasia, pallor, and increased cup-to-disk ratio.7

So far, the risk to developing fetuses does not seem to be specific to a particular period of pregnancy. Thus, to prevent microcephaly with its attendant neurologic and ocular problems, pregnant women should avoid bites from mosquitoes that might be carrying Zika virus. How should this be done? Most everyone agrees that insect repellents should be used and mosquito populations should be reduced in Zika-active areas through environmental control and/or the use of insecticides. The CDC advises pregnant women (and women who might soon become pregnant) to avoid travel to areas where Zika is circulating.3 Some countries (including Brazil, Colombia, Ecuador, El Salvador, and Jamaica) have recommended that women residing there avoid becoming pregnant — with El Salvador suggesting women not get pregnant until at least 2018.4 Whether families choose such extreme measures or not, attention to mosquito control is essential.

Transmission of Zika virus is also possible via blood transfusions and, potentially, through sexual contact. Pregnant women requiring transfusions should, when possible, receive blood from donors who were not recently in Zika-active areas. Even without clear evidence available yet, Public Health England has advised male travelers to Zika-active areas to use condoms for 28 days following travel if their partner is at risk of pregnancy and to use condoms for 6 months if they become ill with Zika infection.2 If and as Zika virus becomes established in parts of the Americas, and as preventive and therapeutic interventions develop, practical adjustments in travel plans and risk avoidance will need to be updated.

REFERENCES

  1. Hayes EB. Zika virus outside Africa. Emerg Infect Dis 2009;15:1347-1350.
  2. Gulland A. Zika virus is a global public health emergency, declares WHO. BMJ 2016;352:i657.
  3. Centers for Disease Control and Prevention. Zika Virus. www.cdc.gov/zika. Accessed Feb. 10, 2016.
  4. Higgs S. Zika virus: Emergence and emergency. Vector-Borne Zoonotic Dis 2016;16:75-76.
  5. Centers for Disease Control and Prevention. Approximate distribution of Aedes aegypti and Aedes albopictus in the United States. www.cdc.gov/chikungunya/resources/vector-control.html. Accessed Feb. 10, 2016.
  6. Schuler-Faccini L, Ribeiro EM, Feitosa IM, et al. Possible association between Zika virus infection and microcephaly — Brazil, 2015. MMWR 2016;65:59-62.
  7. Ventura CV, Maia M, Ventura BV, et al. Ophthalmological findings in infants with microcephaly and presumable intra-uterus Zika virus infection. Arq Bras Oftalmol 2016;79:1-3.